Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons |
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Authors: | Luca Avenali Oli Abate Fulas Julia Sondermann Pratibha Narayanan David Gomez-Varela |
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Affiliation: | Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group, Goettingen, Germany |
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Abstract: | The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling. Here we show that the neuropeptide Nocistatin sensitizes TRPA1-dependent calcium influx upon application of the TRPA1 agonist mustard oil (MO) in cultured sensory neurons of dorsal root ganglia (DRG). Interestingly, TRPV1-mediated cellular calcium responses are unaffected by Nocistatin. Furthermore, Nocistatin-induced TRPA1-sensitization is likely independent of the Nocistatin binding partner 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) as assessed by siRNA-mediated knockdown in DRG cultures. In conclusion, we uncovered the sensitization of TRPA1 by Nocistatin, which may represent a novel mechanism how Nocistatin can modulate pain. |
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Keywords: | NIPSNAP1 nociception Nocistatin peripheral sensory neurons sensitization TRPA1 |
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